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Background

Genome-wide association studies (GWASs) have shown that genetic variants are important determinants of free fatty acid levels. The mechanisms underlying the associations between genetic variants and free fatty acid levels are incompletely understood. Here, we aimed to identify genetic markers that could influence diverse fatty acid levels in a Chinese population and uncover the molecular mechanisms in terms of DNA methylation and gene expression.

Results

We identified strong associations between single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) region and multiple polyunsaturated fatty acids. Expression quantitative trait locus (eQTL) analysis of rs174570 on FADS1 and FADS2 mRNA levels proved that minor allele of rs174570 was associated with decreased FADS1 and FADS2 expression levels (P < 0.05). Methylation quantitative trait locus (mQTL) analysis of rs174570 on DNA methylation levels in three selected regions of FADS region showed that the methylation levels at four CpG sites in FADS1, one CpG site in intragenic region, and three CpG sites in FADS2 were strongly associated with rs174570 (P < 0.05). Then, we demonstrated that methylation levels at three CpG sites in FADS1 were negatively associated with FADS1 and FADS2 expression, while two CpG sites in FADS2 were positively associated with FADS1 and FADS2 expression. Using mediation analysis, we further show that the observed effect of rs174570 on gene expression was tightly correlated with the effect predicted through association with methylation.

Conclusions

Our findings suggest that genetic variants in the FADS region are major genetic modifiers that can regulate fatty acid metabolism through epigenetic gene regulation."xsd:string
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http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/author"He Z."xsd:string
http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/author"Jin L."xsd:string
http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/author"Jiang F."xsd:string
http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/author"Zhang H."xsd:string
http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/author"Zhang R."xsd:string
http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/author"Xu B."xsd:string
http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/author"Wang T."xsd:string
http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/author"Zhao A."xsd:string
http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/author"Hu C."xsd:string
http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/author"Jia W."xsd:string
http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/author"Jia W.'"xsd:string
http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/name"Clin Epigenetics"xsd:string
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http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/title"FADS1-FADS2 genetic polymorphisms are associated with fatty acid metabolism through changes in DNA methylation and gene expression."xsd:string
http://purl.uniprot.org/citations/30157936http://purl.uniprot.org/core/volume"10"xsd:string
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